Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia

Ryu Okumura, Takashi Kurakawa, Takashi Nakano, Hisako Kayama, Makoto Kinoshita, Daisuke Motooka, Kazuyoshi Gotoh, Taishi Kimura, Naganori Kamiyama, Takashi Kusu, Yoshiyasu Ueda, Hong Wu, Hideki Iijima, Soumik Barman, Hideki Osawa, Hiroshi Matsuno, Junichi Nishimura, Yusuke Ohba, Shota Nakamura, Tetsuya IidaMasahiro Yamamoto, Eiji Umemoto, Koichi Sano, Kiyoshi Takeda

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Colonic epithelial cells are covered by thick inner and outer mucus layers. The inner mucus layer is free of commensal microbiota, which contributes to the maintenance of gut homeostasis. In the small intestine, molecules critical for prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti-microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have been identified7-11. Although there are mucus layers providing physical barriers against the large number of microbiota present in the large intestine, the mechanisms that separate bacteria and colonic epithelia are not fully elucidated. Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively expressed in epithelial cells at the uppermost layer of the large intestinal gland, was secreted into the lumen and bound flagellated bacteria including Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner mucus layer and many flagellated bacteria invaded epithelia. Lypd8-/- mice were highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the bacterial-free state of the inner mucus layer and ameliorated DSS-induced intestinal inflammation in Lypd8-/- mice. Lypd8 bound to flagella and suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of intestinal bacteria and epithelial cells in the colon to preserve intestinal homeostasis.

Original languageEnglish
Pages (from-to)117-121
Number of pages5
JournalNature
Volume532
Issue number7597
DOIs
Publication statusPublished - Apr 7 2016

ASJC Scopus subject areas

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    Okumura, R., Kurakawa, T., Nakano, T., Kayama, H., Kinoshita, M., Motooka, D., Gotoh, K., Kimura, T., Kamiyama, N., Kusu, T., Ueda, Y., Wu, H., Iijima, H., Barman, S., Osawa, H., Matsuno, H., Nishimura, J., Ohba, Y., Nakamura, S., ... Takeda, K. (2016). Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. Nature, 532(7597), 117-121. https://doi.org/10.1038/nature17406